xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated trem2+ macrophages

异种肌肤移植经过激活的trem2+巨噬细胞推进血管生成和组织再生

skin allo- and xenotransplantation are the standard treatment for major burns when donor sites for autografts are not available.

当自体移植供体部位不可以用时，同种异体和异种肌肤移植是严峻烧伤的标准医治办法。

the relationship between the immune response to foreign grafts and their impact on wound healing has not been fully elucidated.

对外来移植物的免疫反应及其对伤口愈合的影响之间的联络没有完全阐明。

here, we investigated changes in collagen architecture after xenogeneic implantation of human biologic scaffolds.

在这儿，咱们研讨了异栽培入人体生物支架后胶原规划的改变。

we show that collagen deposition in response to the implantation of human split-thickness skin grafts (hstsgs) containing live cells recapitulates normal skin architecture, whereas human acellular dermal matrix (adm) grafts led to a fibrotic collagen deposition.

咱们标明，植入富含活细胞的人割裂厚度肌肤移植物后，胶原堆积恢复正常肌肤规划，而人脱细胞真皮基质移植物致使纤维化胶原堆积。

we show that macrophage differentiation in response to hstsg implantation is driven toward regenerative trem2+ subpopulations and found that hydrogel delivery of these cells significantly accelerated wound closure.

咱们标明，巨噬细胞对hstsg植入的反应分化被驱意向再生的trem2+亚群，并发现这些细胞的水凝胶投递显着加速了伤口闭合。

our study identifies the preclinical therapeutic potential of trem2+ macrophages to mitigate fibrosis and promote wound healing, providing a novel effective strategy to develop advanced cell therapies for complex wounds.

咱们的研讨断定了trem2+巨噬细胞减轻纤维化和推进伤口愈合的临床前医治潜力，为开发凌乱伤口的领先细胞疗法供给了一种新的有用战略。

要点词汇

xenogeneic异种的；异基因的

xenotransplantation异种移植

standard treatment标准待遇；标准医治；标准处置

autografts同体移植物（如肌肤、组织等）；（autograft的复数）

grafts移植；嫁接；贪婪；(graft的第三人称奇数)；不尽职；(graft的复数)

wound healing伤口愈合；创面愈合；伤口愈合

elucidated阐明；说明；（elucidate的曩昔式和曩昔分词）

scaffolds脚手架；支架；断头台；（scaffold的复数）

acellular无细胞的；非细胞的；单细胞的

fibrotic纤维化的；[医]纤维变性的

for more than 50 years, transplantation of unmatched human skin grafts has been the clinical standard of care for major burn wounds when autologous skin grafts are not available because of the extent of the burn injury.

50多年来，当因为烧伤的程度而无法获得自体肌肤移植物时，移植无与伦比的人类肌肤移植物一向是医治严峻烧伤的临床标准。

although the cellular elements of unmatched grafts are rejected by the host, extracellular matrix

(ecm) elements integrate into the wound bed and are potentially beneficial to wound healing in patients with burnsand chronic wounds.

尽管不匹配的移植物的细胞成分被宿主架空，但细胞外基质(ecm)成分联系到伤口床中，并对烧伤弛缓慢伤口患者的伤口愈合具有潜在的优点。

in mice, it has been shown that the implantation of xenogeneic dermal scaffolds does not induce a strong inflammatory response but has a strong impact on macrophage polarization, potentially inducing regenerative phenotypes.

在小鼠中，现已标明异种真皮支架的植入不会诱导激烈的炎症反应，可是对巨噬细胞极化有激烈的影响，潜在地诱导再生表型。

要点词汇

unmatched不相配的；不配对的；无与伦比的

grafts移植；嫁接；贪婪；(graft的第三人称奇数)；不尽职；(graft的复数)

burn wounds烧伤创面；烧伤伤口；烧烫坏创面

extracellular matrix细胞外基质

integrate into联系到；融入；集成到

wound healing伤口愈合；创面愈合；伤口愈合

xenogeneic异种的；异基因的

dermal真皮的；肌肤的

scaffolds脚手架；支架；断头台；（scaffold的复数）

phenotypes显型；表面型；（phenotype的复数）

macrophages are a heterogeneous and highly plastic cell population and believed to be critical mediators of the cellular response during all stages of soft tissue injury.

巨噬细胞是一种异质性和高度可塑性的细胞群，被认为是软组织损害一切期间细胞反应的要害介质。

traditional classification systems of macrophages describe “classically activated” m1 macrophages, dominating the acute inflammation stage after injury, and “alternatively activated” m2 macrophages, which are thought to be involved in reparative processes of soft tissue remodeling.

巨噬细胞的传统分类体系描绘了“经典激活”的m1巨噬细胞，在损害后的急性炎症期间占主导方位，以及“替换激活”的m2巨噬细胞，它们被认为参加软组织重塑的批改进程。

these classifications, however, were derived from in vitro studies and have been shown

to insufficiently characterize the broad spectrum of macrophage phenotypes found in physiologic and pathologic conditions in vivo.

可是，这些分类来历于体外研讨，并已被证明缺乏以表征在体内生理和病理条件下发现的广谱巨噬细胞表型。

implantation of both synthetic and biological materials induces specific tissue microenvironments that likely drive macrophage subpopulations.

组成和生物材料的植入诱导可以驱动巨噬细胞亚群的特定组织微环境。

synthetic materials commonly instigate a proinflammatory response, whereas biological grafts can induce regenerative macrophage subpopulations, potentially suppressing the development of fibrosis by producing arginase 1 (arg1), resistin-like molecule-α (relmα), and interleukin-10 (il-10).

组成材料一般引发促炎反应，而生物移植物可以诱导再生巨噬细胞亚群，经过发生精氨酸酶1 (arg1)、反抗素样分子-α (relmα)和白细胞介素-10 (il-10)潜在地抑制纤维化的打开。

to add to the complexity, other studies have suggested a profibrotic role for “m2” macrophages because of their ability to stimulate fibroblast differentiation into myofibroblasts.

更凌乱的是，其他研讨标明“m2”巨噬细胞具有促纤维化作用，因为它们可以影响成纤维细胞分化为肌成纤维细胞。

collectively, these findings indicate that the impact of macrophage heterogeneity on the process of wound repair and tissue fibrosis remains incompletely understood.

总的来说，这些发现标明巨噬细胞异质性对伤口批改和组织纤维化进程的影响仍不完全理解。

要点词汇

be critical至关重要；非常要害

soft tissue injury软组织损害；软组织外伤；软组织损害

classically古典主义地；拟古地

dominating分配；控制；（dominate的如今分词）；独裁的；专横的；首要的；控制的

reparative抵偿的；修缮的；抵偿的；修补的

insufficiently不可地；不能担任地

broad spectrum广谱；宽光谱

macrophage巨噬细胞

phenotypes显型；表面型；（phenotype的复数）

physiologic生理的；生理学的

here, we examine the impact of clinically used human biologic scaffolds on the innate immune response and wound healing over time in a murine model.

在这儿，咱们研讨了在鼠模型中临床运用的人类生物支架对先天免疫反应和伤口愈合随时刻的影响。

using single-cell rna sequencing (scrna-seq), we show that macrophage polarization in response to cellular human split-thickness skin grafts (hstsgs) is driven toward a distinct subpopulation characterized by a high expression of the lipid receptor trem2 (triggering receptor expressed on myeloid cells) as well as proangiogenic and antifibrotic gene expression profiles.

运用单细胞rna测序(scrna-seq)，咱们标明巨噬细胞极化对细胞人类割裂厚度肌肤移植物(hstsgs)的反应被驱意向一个一起的亚群，其特征是脂质受体trem2(髓样细胞上表达的触发受体)的高表达以及促血管生成和抗纤维化基因表达谱。

we then confirmed that vitamin d (vd) signaling drives clonal proliferation of myeloid cells during skin healing using myeloid cell–specific cre-mediated recombination in a multicolor reporter mouse model.

然后，咱们在多色陈述小鼠模型中运用骨髓细胞特异性cre介导的重组证明晰维生素d (vd)信号传导在肌肤愈合进程中驱动骨髓细胞的克隆增殖。

last, we developed an approach to induce regenerative trem2+ transcriptomic programs in vitro by treating bone marrow (bm)–derived macrophages with vitamin d3 (vd3; 1,25-dihydroxycholecalciferol) and showed that trem2+ macrophages significantly accelerate the healing of murine full-thickness excisional wounds.

最终，咱们开发了一种办法，经过用维生素d3(vd3；1，25-二羟基胆钙化醇)，并闪现trem2+巨噬细胞显着加速小鼠全层切除伤口的愈合。

要点词汇

biologic生物学的；生物的

scaffolds脚手架；支架；断头台；（scaffold的复数）

innate天然生成的；生来的；先天的；天资的

wound healing伤口愈合；创面愈合；伤口愈合

macrophage巨噬细胞

grafts移植；嫁接；贪婪；(graft的第三人称奇数)；不尽职；(graft的复数)

subpopulation（从其别人员分出或构成总人员的）分组人员

myeloid骨髓的；脊髓的；骨髓性的

clonal[生]无性（繁衍）系的；无性（繁衍）系般的

multicolor五颜六色绚丽的；多色的；多色

trem2+ macrophages have previously been shown to be involved in lipid metabolism and the regulation of hair follicle stem cell activity, pointing to an important role in skin regeneration.

trem2+巨噬细胞早年已被证明参加脂质代谢和毛囊干细胞活性的调度，标明其在肌肤再生中的重要作用。

moreover, the regenerative action of trem2+ macrophages has been previously corroborated in other organ systems, such as during colonic mucosal healing or liver regeneration where trem2+ macrophages promote regenerative endothelial cell differentiation.

此外，trem2+巨噬细胞的再生作用早年现已在其他器官体系中得到证明，例如在结肠粘膜愈合或肝脏再生时刻，其间trem2+巨噬细胞推进再生内皮细胞分化。

variants in the trem2 locus are associated with early-onset alzheimer’s disease in humans, related to a reduced clearance of extracellular amyloid β–containing plaques due to an impaired function of microglia within the brain.

trem2基因座的变异与人类早发性阿尔茨海默病有关，这与大脑内小胶质细胞功用受损致使细胞外含淀粉样β蛋白斑块铲除减稀有关。

in mouse models of alzheimer’s disease, enhancement of trem2 signaling using agonistic antibodies has recently shown beneficial effects on cognitive function through attenuation of neuroinflammation and improved plaque clearance within the brain.

在阿尔茨海默病的小鼠模型中，运用激动性抗体增强trem2信号迩来闪现出经过减轻神经炎症和改进大脑内斑块铲除对认知功用的有利作用。

the accelerated healing rates after enrichment of the wound bed with trem2+ macrophages that we observed in our study might be due to a more efficient phagocytosis of dead cells and debris within the wound.

咱们在研讨中调查到的伤口床富含trem2+巨噬细胞后愈合速度加速可所以因为伤口内去世细胞和碎片被更有用地吞噬。

moreover, proangiogenic growth factors secreted by trem2+ macrophages may improve vascularization and oxygen supply required for wound healing.

此外，trem2+巨噬细胞分泌的促血管生成生长因子可以改进伤口愈合所需的血管构成和氧气供给。

要点词汇

hair follicle毛囊；毛发毛囊

corroborated证明；（corroborate的曩昔式）

colonic结肠的；影响结肠的；灌肠

endothelial cell内皮细胞

variants变体；变种；变量；（variant的复数）

locus方位；点；地址；轨迹；笼统事物的中心；位点

amyloid淀粉样蛋白

plaques血小板；（plaque的复数）

microglia小神经胶质

agonistic好辩的；好斗的；敌对的；振奋剂的；用作振奋剂的

our study uncovers the molecular background driving the long observed beneficial effects of unmatched skin transplantation on wound healing. we demonstrate the preclinical therapeutic potential of trem2+ macrophages to mitigate fibrosis and promote wound healing.

咱们的研讨提示了推进长时刻调查到的无与伦比的肌肤移植对伤口愈合的有利作用的分子布景。咱们证明晰trem2+巨噬细胞在减轻纤维化和推进伤口愈合方面的临床前医治潜力。

we show that regenerative trem2+ macrophages can be externally derived from bm cells in vitro using vd3 and then exogenously applied to wounds as a cell-based therapy.

咱们标明，再生的trem2+巨噬细胞可以在体外运用vd3从骨髓细胞中获得，然后作为一种根据细胞的疗法外源性地使用于伤口。

要点词汇

uncovers掀开；戳穿

unmatched不相配的；不配对的；无与伦比的

wound healing伤口愈合；创面愈合；伤口愈合

preclinical临床前的；临床实习前的；临症前期的；临床运用前的

mitigate使温文；使陡峭；减轻

fibrosis纤维化；纤维变性

healing治好；（heal的如今分词方法）；康复；有医治功用的；恢复；恢复

regenerative再生的；更生的；再生式制动的；反应式制动的

externally表面上；外部地

wounds伤口；（wound的复数）；使受伤；（wound的第三人称奇数）；受伤，损伤

our approach to induce trem2+ macrophages and deliver them to the wound bed using hydrogels provides a novel, effective strategy with a high potential for clinical translation.

咱们诱导trem2+巨噬细胞并运用水凝胶将它们投递到伤口床的办法供给了一种新的、有用的战略，具有很高的临床转化潜力。

in the clinic, myeloid cells can be readily obtained in high quantities from the peripheral blood using clinically established cell apheresis and culture protocols, stimulated to differentiate into trem2 phenotypes with vd3, and easily integrated with the current standard of care to improve wound healing after injury.

在临床上，运用临床树立的细胞别离和培育方案，可以简略地从外周血中许多获得髓样细胞，用vd3影响其分化为trem2表型，而且简略与其时的维护标准相联系，以改进损害后的伤口愈合。

要点词汇

induce劝使；引诱；致使；致使；致使；引产；致使流产；归纳出；感应；感生

high potential高潜力；高潜能；高电位

myeloid骨髓的；脊髓的；骨髓性的

readily毫不犹疑地；心甘情愿地；愿意地；怅然地；简略地；灵敏地；无困难地；不推迟地

clinically临床医学地；临床地；镇定高效地；有用地；洁净地

apheresis词首音掉落；单采血液成分法；获取法；别离性输血

stimulated煽动；鼓励；影响；（stimulate的曩昔式和曩昔分词）；起影响作用；起推进作用；遭到影响的；遭到煽动的

differentiate差异；区别；变异；改变；求…的微分；区分；使不一样；使有不一样

phenotypes显型；表面型；（phenotype的复数）

wound healing伤口愈合；创面愈合；伤口愈合

根据多年的言语学习实习，发现，跟着社会的飞速打开，英语、汉语等重要言语也在不断的与时俱进。这个时分，咱们以不变应万变的办法之一，可所以阅览干流刊物。

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主张我们在阅览这篇文章时：第一遍快速阅览，领会文章要点，晓得粗心；第二遍初步精读，每看完一段，要细心领会其间每一句在期间中的功用，各句之间的联络，这一段是如何联接上下文的，它在整个语篇中的方位，以前进你猜测词义和推理上下文才能；第三遍可以查看中英翻译，持续从微观到微观地了解原文，学会区别要点和非有必要信息（这对考试时的阅览非常重要），总结词汇，分配和句型，而且最佳单独翻译一遍原文，以进一步加强了解。

最终主张我们要学致使用，使用从文章大学到的词汇，分配，句型以及长难句规划进行造句，前进英文写作才能。

学习途径主张：金句回想——要害词学习——拓宽词汇练习——触类旁通——触类旁通。

温馨提示：阅览完看着中文译文自个着手翻译出英文，然后将您译的英文与原文进行比照，以此来前进英文表达和语句规划的精确性和地道性。